{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:18:10Z","timestamp":1784002690865,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2023MC013"],"award-info":[{"award-number":["ZR2023MC013"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2024QC193"],"award-info":[{"award-number":["ZR2024QC193"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Postdoctoral Innovation Program of Shandong Province","award":["SDCX-ZG-202303003"],"award-info":[{"award-number":["SDCX-ZG-202303003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nonsense-mediated mRNA decay (NMD) is a highly conserved RNA quality and quantity surveillance machinery in eukaryotic cells, serving as an important node in the post-transcriptional gene expression. Previous studies using the complete knockout of individual NMD factors in cells or animals reveal that NMD deficiency causes developmental defects and compromises tissue homeostasis. However, because most NMD factors participate in multiple molecular functions, a direct link between NMD and cell fate determination is missing. SMG6 is a core NMD effector and the only endoribonuclease among all NMD factors. The NMD function of SMG6 is exclusively mediated by its PIN (PilT N-terminus) domain. In this study, we engineered a mouse model with the capability of specifically deactivating the SMG6\u2019s PIN domain\/endoribonuclease activity (Smg6-PINF\/F), but not knocking out the complete SMG6 protein. We found that SMG6\u2019s PIN domain is essential for NMD activity in embryonic stem cells (ESCs) and various tissues of adult mice. Furthermore, loss of SMG6\u2019s PIN domain is dispensable for the mouse ESC self-renewal, but severely compromises the differentiation, which consequently causes the mutant mice to die during the process of organogenesis. Through the induced deletion of SMG6\u2019s PIN domain in adult mice, we found that loss of SMG6\u2019s NMD function affects the homeostasis of several mouse tissues, including the testis and the intestine. In sum, our study establishes a mechanistic link between NMD per se and cell fate determination of mouse ESCs, as well as in the tissues of adult mice, where cell fate transitions are actively ongoing. The Smg6-PINF\/F mouse line could be a valuable strain for elucidating the biology of NMD per se.<\/jats:p>","DOI":"10.3390\/cells15030282","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:49:44Z","timestamp":1770036584000},"page":"282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SMG6\u2019s PIN (PilT N-Terminus) Domain Is Required for Nonsense-Mediated mRNA Decay (NMD) In Vivo"],"prefix":"10.3390","volume":"15","author":[{"given":"Baihui","family":"Chai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"},{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"},{"name":"College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-9166","authenticated-orcid":false,"given":"Tangliang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao 266237, China"},{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrm4063","article-title":"Nonsense-mediated mRNA decay: An intricate machinery that shapes transcriptomes","volume":"16","author":"Jensen","year":"2015","journal-title":"Nat. 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